1. Field of the Invention
The present invention relates to prepackaged therapeutic regimens for the symptomatic treatment of individuals with rhinitis, which combine decongestant and antihistamine medications in a manner to avoid daytime sedation and minimize stimulation from decongestants.
2. Description of the Prior Art
Rhinitis refers to an inflammatory disorder of the nasal passages. The symptoms of rhinitis typically consist of sneezing, rhinorrhea, nasal congestion, and increased nasal secretions. Failure of treatment of rhinitis may lead to other disorders including infection of the sinuses, ears and lower respiratory tract.
Two types of oral medication are commonly used to treat rhinitis: decongestants and antihistamines. Decongestants and antihistamines differ in mechanism of action, therapeutic effects and side effects. It is common practice to combine the use of these two to bring about more complete symptom relief of rhinitis than with either entity alone.
Decongestants act to constrict vessels in the nasal mucus membranes and thereby decrease tissue swelling and nasal congestion. They are known to open congested nasal airways more effectively than antihistamines. Examples of oral nasal decongestants include pseudoephedrine and phenylephrine. Nasal decongestants are adrenalin-like, and therefore stimulatory. Their therapeutic effect may be accompanied by side effects of irritability, hyperactivity, and restlessness. At night they are known to produce insomnia. Susceptibility to the stimulatory effect of decongestants is known to vary widely among individuals. Some individuals tolerate these agents well, while others encounter varying degrees of intolerance. In some instances, individuals are able to tolerate the stimulatory effects while active, as during the day, but not a night, when they interfere with sleep.
Histamine is a mediator released from cells that line the walls of the nasal mucous membranes (mast cells). When released, histamine is known to bind to local receptors and cause sneezing, nasal itching, swelling of the nasal membranes, and increased nasal secretions. Antihistamines block the binding of histamine to histamine receptors in the nasal membranes and preempt the precipitation of these symptoms by histamine release. Although individuals typically take antihistamines after symptoms occur, it is more desirable to dose antihistamine so as to effect therapeutic availability in anticipation of the peak times of histamine release, typically in the early morning hours in allergic rhinitis. Antihistamines are known to be sedating. To improve upon this, newer antihistamines with no or little sedation have been developed.
Decongestants and antihistamines have been formulated into single dosage units to offer more complete relief of rhinitis symptoms than therapy with either component alone. The incorporation of stimulating decongestant and sedating antihistamine into a single dosage unit represents an attempt to balance stimulation and sedation of the components. As noted, individuals vary in their susceptibility to side effects, and some individuals experience irritability, sedation, or both when taking these combinations. Formulations containing decongestant and sedating antihistamine are exemplified by:
CHLOR-TRIMETON® 4 hour Allergy/Decongestant which contains 4 mg of chlorpheniramine (sedating antihistamine) and 60 mg pseudoephedrine sulfate (stimulating decongestant), and which is recommended to be taken every 4-6 hours (½ this dosage for children 6 to under 12).
BROMFED® Tablets which contains 4 mg of brompheniramine (sedating antihistamine) and 60 mg pseudoephedrine sulfate (stimulating decongestant), and which is recommended to be taken every 4-6 hours (½ this dosage for children 6 to under 12).
BENADRYL® Allergy Decongestant Tablets which contains 25 mg of diphenhydramine hydrochloride (sedating antihistamine) and 60 mg pseudoephedrine sulfate (stimulating decongestant), and which is recommended to be taken by adults and children over 12 years of age every 4-6 hours, not to exceed 4 tablets in 24 hours.
TAVIST-D® Tablets which contains 1.34 mg clemastine fumarate (sedating antihistamine) and 75 mg phenylpropanolamine hydrochloride (stimulating decongestant), and which is recommended to be taken every 12 hours (adults and children over 12 years of age only).
Formulations have also been commercialized which incorporate a decongestant and a non-sedating antihistamine into a single dosage unit. Such combinations would be expected, in general, to be more stimulating than combinations, which employ a sedating antihistamine that might counter the effects of stimulation caused by the decongestant. Examples of such formulations include:
CLARITIN-D® 24 HOUR Extended-Release Tablets which contains 10 mg loratidine (antihistamine) and 240 mg pseudoephedrine hydrochloride (decongestant) and which is recommended to be taken every 24 hours (adults and children over 12 years of age).
ALLEGRA-D™ containing 60 mg fexofenadine (non-sedating antihistamine) and 120 mg pseudoephedrine hydrochloride (stimulating decongestant) and which is recommended for every 12 hours (adults and children over 12 years of age).
All of the single dosage units described are instructed, by their manufacturers, for use around the clock. U.S. Pat. No. 4,295,567 (Knudsen) teaches a packaged regimen which provides and instructs use of sedating antihistamine only at night in order to avoid daytime sedation from antihistamine. Knudsen does not address the stimulatory side-effects of decongestants. Particularly, Knudsen contains no teaching to avoid the stimulating side effects from decongestants that can occur when antihistamines and decongestants are used together.
Regimens have been commercialized which incorporate a decongestant for daytime and not for nighttime. An example of one such prepackaged regimen is SYN-RX™ , which contains 60 mg pseudoephedrine HCL and 600 mg Guaifenesin in the day formulation and 600 mg of guaifenesin in the nighttime formulation. These regimens avoid stimulation from decongestant at night, however lack antihistamine. Further, they neither contain medication which would be effective for rhinitis symptoms at night, nor anticipate peak symptoms of rhinitis in the morning hours on awakening.
It is well known that individuals with rhinitis utilize antihistamines and decongestants together hundreds of millions of times a year, often encountering undesired side effects. While it is desirable to take advantage of the therapeutic benefits of decongestant medications for rhinitis, there is a present need for regimens which advantageously use antihistamines and decongestants in a manner to minimize the side effects of decongestants as well as antihistamines, particularly regimens which fulfill individual needs in accord with individual variations in susceptibility to side effects of decongestants.
Prevention of medication error is a considerable problem and is improved with measures to establish simplicity, reduce confusion, and increase convenience. The proposed use of a multiplicity of dosage units as a regimen may be associated with dosage units being confused with each other, inadvertently switched, lost, misplaced, or ignored. Another problem associated with treatment using a plurality of units is the lack of indicia which distinguish the dosage units from each other and signify and verify their use together. Yet another problem is the lack of readily available instructions for coordinating the medications. Individuals are known to lose instructions issued separate from medication in its immediate container. Haphazard selection and organization of medications can result in treatment failure and in the patient's requiring additional medical attention involving time, expense and personnel costs and effort to instruct the patient and organize therapy. Cost factors and outcomes are being carefully considered in the current medical climate. Improvements in organization and teaching including devices and methods which would help patients be more cognizant of their proper therapeutic requirements are considered desirable in view of limitations in time and costs for medical personnel. Successful therapy for rhinitis is less costly than unsuccessful treatment that eventuates in complications or multiple clinic visits.